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Related Experiment Video

Updated: May 22, 2025

Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
09:41

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Published on: February 25, 2021

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Optimizing Microfluidic Channel Design with Tilted Rectangular Baffles for Enhanced mRNA-Lipid Nanoparticle

Mingzhi Yu1, Dongsheng Liu2,3, Pranay Shah1

  • 1Centre of Micro/Nano Manufacturing Technology (MNMT-Dublin), School of Mechanical & Materials Engineering, University College Dublin, Dublin 4 D04 V1W8, Ireland.

ACS Biomaterials Science & Engineering
|May 21, 2025
PubMed
Summary

Researchers optimized microfluidic chips for producing lipid nanoparticles (LNPs) for RNA therapeutics. A 70° baffle angle and 150 µm length design improved LNP production and transfection efficiency.

Keywords:
CFD simulationslipid nanoparticlesmicrofluidictransfection

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Area of Science:

  • Biotechnology
  • Materials Science
  • Chemical Engineering

Background:

  • RNA therapeutics offer novel treatment strategies but face challenges in stability and delivery.
  • Lipid-based nanoparticles (LNPs) are essential for encapsulating and delivering RNA payloads.
  • Microfluidic fabrication offers precise control for LNP production.

Purpose of the Study:

  • To design, simulate, and optimize microfluidic chip configurations for efficient LNP fabrication.
  • To identify optimal microfluidic channel designs for high mixing efficiency and scalability in LNP production.
  • To validate simulation findings through experimental fabrication and assess LNP transfection efficiency.

Main Methods:

  • Computational fluid dynamics (CFD) simulations were used to evaluate various microfluidic channel designs with flow focusing and tilted rectangular baffles.
  • Poly(dimethylsiloxane) (PDMS) microfluidic chips were fabricated based on simulation results.
  • Lipid nanoparticles (LNPs) encapsulating green fluorescent protein mRNA (GFP mRNA) were prepared and their transfection efficiency was evaluated *in vitro*.

Main Results:

  • Microfluidic channels with baffle angles between 70-90° showed high mixing efficiency.
  • A 70° baffle angle and 150 µm baffle length provided optimal mixing and acceptable pressure drop.
  • The optimal microfluidic design yielded LNPs with the highest *in vitro* transfection efficiency at an N/P ratio of 5.6.

Conclusions:

  • Optimized microfluidic chip design enhances LNP production for RNA therapeutics.
  • The developed method offers a scalable and reproducible approach for LNP fabrication.
  • This research facilitates the clinical translation of RNA-based medicines.